Over the next 5 years, the main objective of this project will be to isolate and analyze specific visual system mutations in zebrafish. Mutations are induced in zebrafish by exposing males to ethylnitrosurea, and recessive mutations are looked for in third-generation fish bred from second-generation siblings. Visual defects are detected using an optokinetic response test, i.e., the ability of the eye to follow a moving striped pattern. Four specific aims are proposed: (1) to produce mutant fish that have a variety of visual system defects of interest to many visual system researchers; as mutant fish are uncovered and classified, these fish will be made available to interested parties; (2) to develop more sophisticated behavioral tests that will enable the uncovering of mutants specific to the visual system; in particular, behavioral tests that uncover visual system mutants in animals that are morphologically normal will be sought; (3) to analyze selected mutants at a cellular and molecular level in order to uncover ultimately the specific gene mutated, its protein product and the role of the gene and its product in retinal function, employing electrophysiological as well as cellular and molecular biological techniques initially to analyze these mutants; and (4) to continue studies on normal (wild-type) retinal structure, function and development in zebrafish as background for the analysis of mutant fish.